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Macrophages were first discovered in 1882 when Elia Metchnikoff recognized them as important phagocytic cells that can engulf any foreign material, including fungal spores. This discovery has proved to be a milestone in establishing the field of innate immunity. Macrophages are still ruling the area after 140 years of their discovery. This book explores the diverse role of macrophages in vertebrate immunity, parasitic, bacterial, and viral infections, regeneration, inflammation, and neurological diseases.

Macrophages.

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Macrophages were first discovered in 1882 when Elia Metchnikoff recognized them as important phagocytic cells that can engulf any foreign material, including fungal spores. This discovery has proved to be a milestone in establishing the field of innate immunity. Macrophages are still ruling the area after 140 years of their discovery. This book explores the diverse role of macrophages in vertebrate immunity, parasitic, bacterial, and viral infections, regeneration, inflammation, and neurological diseases.

Macrophages --- Macrophages --- Activation. --- Research --- Methodology.

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Macrophages were first discovered in 1882 when Elia Metchnikoff recognized them as important phagocytic cells that can engulf any foreign material, including fungal spores. This discovery has proved to be a milestone in establishing the field of innate immunity. Macrophages are still ruling the area after 140 years of their discovery. This book explores the diverse role of macrophages in vertebrate immunity, parasitic, bacterial, and viral infections, regeneration, inflammation, and neurological diseases.

Macrophages --- Activation. --- Research --- Methodology.

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Herpesviridae Infections --- Macrophages --- Lymphocytes --- Mice. --- Disease Models, Animal. --- immunology. --- immunology. --- immunology.

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Le Mésothéliome Pleural Malin (MPM) est un cancer rare et agressif se développant au niveau des cellules mésothéliales de la plèvre. La cause principale du MPM est une exposition antérieure à l’amiante. Actuellement, ce cancer est toujours incurable et les options de traitement sont limitées. Elles comprennent la radiothérapie, la chirurgie, la chimiothérapie et l’immunothérapie. Dans le MPM, des évidences cliniques indiquent que les patients présentant une éosinophilie sanguine périphérique ont un mauvais pronostic. Les macrophages sont des cellules immunitaires qui sont polarisées entre deux phénotypes extrêmes (M1 et M2), en fonction des stimuli perçus dans leur environnement. Les deux phénotypes présentent des fonctions opposées sur la régulation de l’inflammation et de la croissance tumorale. Dans le cas du MPM, l’infiltration et l’accumulation de macrophages associés aux tumeurs est corrélée à un mauvais pronostic. Les objectifs de ce travail de fin d’études sont d’étudier l’effet du surnageant d’éosinophiles sur la polarisation des macrophages et leur cytotoxicité résultante envers les cellules de MPM dans le cadre de l’immunothérapie basée sur les inhibiteurs de points de contrôle. Les résultats démontrent que le surnageant d’éosinophiles mène à la polarisation des macrophages issus de THP-1 vers un phénotype intermédiaire proche des M2. De plus, la culture de macrophages primaires M2 en présence de surnageant d’éosinophiles limite l’efficacité du traitement anti-PD-1. Ces observations peuvent être utiles pour l'amélioration de l'immunothérapie du MPM. Malignant Pleural Mesothelioma (MPM) is a rare and aggressive cancer affecting the mesothelial cells of the pleura. The main cause of MPM is an anterior exposure to asbestos. Nowadays, it is still an incurable cancer and treatment options are rather limited. They include radiotherapy, surgery, chemotherapy, and immunotherapy. Regarding MPM, clinical evidence indicates that patients with peripheral blood eosinophilia present a poorer prognosis. Macrophages are immune cells that polarise between two extreme phenotypes (M1 and M2), depending on the stimuli perceived in their environment. Each phenotype is associated with opposite functions in the regulation of inflammation and tumour growth. In MPM, the infiltration and accumulation of tumour-associated-macrophages in the tumour is associated with a poor prognosis. The aim of this master’s thesis is to study the effect of human eosinophil supernatant onto macrophage polarisation and their resulting cytotoxicity towards MPM cells upon immunotherapy based on immune checkpoint inhibitors. Results demonstrate that eosinophil supernatant leads to the polarisation of THP-1-derived macrophages towards an intermediate phenotype close to M2. Moreover, the culture of M2 primary macrophages with eosinophil supernatant limits the efficiency of the anti-PD-1 treatment. These observations may be useful for the development of improved immunotherapies against MPM.

Mesothelioma --- Macrophages --- Eosinophils --- Immunotherapy --- Cancer --- Sciences de la santé humaine > Oncologie --- Sciences du vivant > Biochimie, biophysique & biologie moléculaire